N (substituted phenyl)-aralkylamines



United States Patent 3,227,757 N (SUBSHTUTED PHENYD-ARALKYLAMINES SidneyB. Richter and David P. Mayer, Chicago, 111., as-

signors to Velsicol Chemical Corporation, Chicago, 1th., a corporationoi Illinois No Drawing. Filed July 10, 1962, Ser. No. 203,907 6 Claims.(Cl. 260570.8)

This invention relates to the production of new pesticidal compositionsof matter. More specifically, this invention relates to new chemicalcompounds of the general formula in which n is a whole number from 1 to3; A, B, C, D, and E are selected from the group consisting of lowerunsubstituted allroxy, chlorine and hydrogen, at least 2 of A, B, C, D,and E are chlorine, a minimum of l and a maximum of 2 of A, B, C, D, andE are lower unsubstituted alkoxy, provided that E is hydrogen when A, B,and C are lower unsubstituted alkoxy, chlorine, and hydrogen,respectively and A is hydrogen when E, D, and C are lower unsubstitutedalkoxy, chlorine and hydrogen, respectively; and R is a phenyl radicalsubstituted with from one to three substituents selected from the groupconsisting of bromine, chlorine, lower substituted alkyl, lowerunsubstituted alkoxy, lower unsubstituted alkylmercapto, hydroxy,mercapto, and nitro. The compounds of this invention can also berepresented by the following general formula:

l I Ill I R; B A

wherein n, A, B, C, D, and E are as defined above, 2 is a whole numberfrom one to three, and R is selected from the group consisting ofbromine, chlorine, lower unsubstituted alkyl, lower unsubstitutedalkoxy, lower unsubstituted alkylmercapto, hydroxy, rnercapto and nitroradicals. By lower alkyl, lower alkoxy, and lower alkylmercapto radicalsare meant those containing up to four carbon atoms. The new compounds ofthis invention are useful as pesticides, particularly as insecticides,rniticides, and herbicides.

The new compounds of this invention can be prepared by the condensationof compounds of the formula I l B A wherein n, A, B, C, D, and E are asdefined above, and Y is chlorine or bromine with amines H NR, wherein Ris also as defined above. Preferred starting materials of the givenformula are those in which n is one and A or B or C is lowerunsubstituted alkoxy. Suitable starting materials of the formula givencan be prepared from the corresponding aldebydes, anhydrides, orcarboxylic acid esters by reduction to the corresponding alcohols followed by treatment with a reagent such as thionyl chloride. For example,reduction of an alkyl ester of a suitably ring-substituted benzoic acidwith lithium aluminum hydride yields the corresponding enzyl alcohol,which can then be treated with thionyl chloride to give theringsubstituted benzyl chloride suitable for use as a starting materialin preparing the compounds of this invention.

3,227,757 Patented Jan. 4, 1966 Suitable starting materials in which nis 2 or 3 can be prepared similarly from the appropriate phenylaceticand phenylpropionic acid esters, respectively.

Some typical carboxylic acids which can be used in the form of theiralkyl esters to be converted to appropriate starting materials for thisinvention include, for example, 2-ethoxy-3,S-dichlorobenzoic acid,2-methoXy-3,5-dichlorophenylacetic acid,3-methoxy2,fi-dichlorophenyl-acetic acid,2,6-dimethoxy-3,S-dichlorobenzoic acid, Z-methoxy- 3,5 dichlorobenzoicacid, 3 methoxy 2,6 dichlorobenzoic acid, 3 methoxy 2,4 dichlorobenzoicacid, 3-methoxy-4,6-dichlorobenzoic acid, 4-methoXy-2,3,5-trichlorobenzoic acid, and the like. Such substituted benzoic acids areknown in the art or can be prepared readily.2-butoxy-3,S-dichlorobenzoic acid, for example, can be obtained from3,5-dichlorosalicylic acid by treatment with butyl bromide in thepresence of silver oxide.

When alkyl esters of these benzoic acids are reduced and chlorinated asdescribed above, the resulting compounds useful as reactants inpreparing the new compounds of the present invention are 2-ethoXy-3,5-dichlorobenzyl chloride, 2 methoxy 3,5 dichlorophenethyl chloride,3-methoXy-2,6-dichlorophenethyl chloride, 2,6-dirnethoxy3,5-dichlorobenzyl chloride, Z-methoxy- 3,5-dichlorobenzyl chloride, 3methoxy 2,6-dichlorobenzyl chloride, 3-methoxy-2,4-dichlorobenzylchloride, 3-methoxy-4,6-dichlorobenzyl chloride, 4-methoXy-2,3,5-trichlorobenzyl chloride, and Z-butoxy 3,5 dichlorobenzyl chloride,respectively.

Suitable reactants of the formula H NR include a wide variety or"anilines substituted with R as defined above. Some typical suitablereactants are, for example, mbromoaniline, p-bromoaniline,2-bromo-4-tert-butylaniline, 2-bromo-4-ethylaniline,5-bromo-2-(ethylthio)aniline, 2-bromo-6-isopropylaniline,2-bromo-4-nitroaniline, rn-butoxyaniline, 2-butoxy-5-nitroaniline,p-tert-butylaniline, 5-butyl-2-chloroani1ine, 5-butyl-2-ethylaniline, 4-butyl3-nitroaniline, m-chloroaniline, 2-chloro-3-nitroaniline,2,4-dibromoaniline, 2,6-dibromo-4-nitroaniline, 2,4- dichloroaniline,2,5-dichloroaniline, 3,4-dichloroaniline, 3,5-dichloroaniline,2,4-dichloro-5-nitroaniline, 2-ethyl-6- nitroaniline,p-(ethylthio)aniline, o-methylthioaniline, mmethylthioaniline,p-methylthioaniline, 2-(rnethylthio)-5- nitroaniline, m-nitroanilinc,o-propoxyaniline, m-propylaniline, p-(propylthio)aniline,2,4,6-tribromoaniline, 2,4,5-trichloroaniline, 2,4,6-trichloroaniline,3,4,5-trichloroaniline, p-(butylthio)aniline, 4-brorno rn anisidine(where anisidine is ar-methoxyaniline), 2-chloro-rn-anisidine,4-chloro-m-anisidine, 6-chloro-m-anisidine, 2-nitrom-anisidine,4-nitro-rn-anisidine, 3-bromo-o-anisidine, 4- chloroo-anisidine,S-chloro-o-anisidine, 3,5 dichloroo-anisidine, 4,S-dichloro-o-anisidine,4-nitro-o-anisidine, 3-bromo-p-anisidine, 3-chloro-p-anisidine,5-chloro-2- nitrop-anisidine, 3,5-dibromo-p-anisidine,3,5-dichloro-panisidine, Z-nitro-p-anisidine, 2-chloro-m-toluidine(where tolnidine is ar-methylaniline), 4-nitro-rn-toluidine, 4-bromo-o-toluidine, 4-chloro-o-toluidine, 4,5-dibromo-otoluidine,4,5-dichloro-o-toluidine, 3-nitro-o-toluidine, 2- brotno-p-toluidine,3-chloro-p-toluidine, 3,5-dibromo-ptoluidine, 3-nitro-p-toluidine,m-aminophenol, o-aminophenol, p-aminophenol, o-aminobenzenethiol,m-aminobenzenethiol, p-aminobenzenethiol, and the like, The designationrnethylthio has been retained for the group CH S, for example, accordingto Chemical Abstracts indexing of such known starting materials.However, it is preferred for the new compounds of this invention to usethe designation methylmercapto for the same group. Other members of thelower alkylmercapto group are named similarly.

When the condensation reaction to form the new compounds of thisinvention is carried out, an excess of the amine should be used, sincethe hydrogen halide released during the reaction is taken up by some ofthe free amine. Preferably two moles of amine are used for each mole ofthe halide starting material. Further, many of the substituted anilinesH NR are not strongly basic, and it is often desirable to incorporate anacid scavenger such as sodium bicarbonate in the reaction mixture. Thereaction can be carried out conveniently by heating the reactants,preferably in an inert solvent such as benzene or toluene. The exactreaction temperatures are not critical, since the reaction will oftentake place at normal room temperature; however, temperatures which arethe normal reflux temperature of the reaction mixture are preferred. Thereaction will often be complete in a few hours. Generally, a precipitateof amine hydrochloride or hydrobromide will form in the reaction mixtureand can be filtered oil. The product can be isolated from the reactionmixture by ether extraction; and it can be purified by crystallization,fractional distillation, or other techniques known to the art. Althoughthe reaction is normally carried out at atmospheric pressure, suborsuperatmospheric pressures can also be used if desired.

The manner in which typical new compounds of this invention can beprepared is illustrated in the following examples. All temperatures arein degrees centigrade.

EXAMPLE 1 Preparation 4-metIz0xy-3,5-diclzlorobenzyl alcohol A solutionof methyl 4-methoxy-3,S-dichlorobenzoate (37.7 g.; 0.16 mole) in 750 m1.ether was added dropwise to a well-stirred slurry of 9 g. lithiumaluminum hydride in 300 ml. ether at such a rate as to maintain gentlereflux. The mixture was refluxed for 1 hr., cooled, and treated dropwiseover a period of 2 hrs. with 250 ml. of H 50 The ether layer was washedwith water, dried over magnesium sulfate, and filtered. Evaporation ofthe ether gave an oil, which was distilled in vacuo to give 24 g. (73%of theory) of 4-methoxy-3,5-dichlorobenzyl alcohol, colorless oil, B.P.126/1.5 mm., which crystallized to a White solid, M.P. 4244.

EXAMPLE 2 Preparation of 4-methoxy-3,5-dichlorobenzyl chloride Thionylchloride (16 g.; 0.14 mole) was added dropwise stirring to4-methoxy-3,S-dichlorobenzyl alcohol (24 g.; 0.11 mole) and pyridine (9g.; 0.11 mole) in 250 ml. toluene. The mixture was stirred and refluxedfor 4 hrs., cooled, and filtered. The solvent and excess thionylchloride were distilled OH, and the residue was distilled in vacuo togive 21 g. (85% of theory) of 4-methoxy-3,5 dichlorobenzyl chloride,pale yellow oil, B.P. 100103/ 0.7 mm., 12 1.5670.

EXAMPLE 3 Preparation of N-(3,4-dichl0roplzenyl)-4-metlz0xy-3,5-dichlorobenzylamine A mixture of 342 g. 3,4-dichloroaniline, 88 g.sodium bicarbonate, and 80 ml. water is stirred and heated to about 80in a 2-1. flask to melt the solid. Liquified 4-methoxy-3,S-dichlorobenzyl chloride (184 g.) is added over a period of0.5 hr., and the mixture is then stirred and refluxed for 7 hrs. Aftercooling, about 500 m1. of ether is added. The ether layer is separated,washed with water, dried over magnesium sulfate, filtered, and evaporated. The residue is fractionally distilled in vacuo. In addition to afraction of any unreacted dichloroaniline (B.P. 102/0.5 mm.), there isobtained as the main fraction the desiredN-(3,4-dichlorophenyl)-4-methoxy-3,5- dichlorobenzylamine.

A wide variety of other useful compounds within the scope of thisinvention can be prepared in a manner similar to that detailed above.Given in the following examples are the reactants which can be used togive the indicated named compounds of this invention.

4 EXAMPLE 4 2-ethoxy-3,S-dichlorobenzyl chloride-l-m-chloroaniline :N-3-chlorophenyl) -2-ethoxy-3,5-dichlorobenzylamine.

EXAMPLE 5 2-methoxy-3,5 dichlorophenethyl chloride-l-p-chloroaniline=N(4-chlorophenyl)-2-methoxy 3,5-dichloro phenethylamine.

EXAMPLE 6 3-methoxy-2,6-dichlorophenethyl chloride|2,5-dimethoxy-4chloroaniline N-(2,5-dimethoxy 4-chlorophenyl-3-methoxy-Z,6-dichlorophenethylamine.

EXAMPLE 7 2,6-dimethoxy-3,5 dichlorobenzylchloride-l-p-methylthioaniline=N (4-methylmercaptophenyl)2,6-dimethoxy-3,5-dichlorobenzylamine.

EXAMPLE 8 Z-methoxy 3,5-dichlorobenzyl chloride+p-anisidine=N(4-methoxyphenyl) 2-methoxy-3,5 dichlorobenzylamine.

EXAMPLE 9 3-methoxy-2,6-dichlorobenzyl chloride-l-p-nitroaniline :N-4-nitrophenyl -3 -methoxy-2,6-dichlorobenzylamine.

EXAMPLE 10 3-methoXy-2,4-dichlorobenzyl chloride-I-3-chloro-p-toluidineN-(3-chloro-4 methylphenyl)-3-methoxy-2,4-dichlorobenzylamine.

EXAMPLE 11 3-methoxy-4,6 dichlorobenzyl chloride-H chloro-panisidine:N(3-chloro-4-methoxyphenyl) 3-methoxy- 4,6-dichlorobenzylamine.

EXAMPLE 12 4-methoxy-2,3,S-trichlorobenzylchloride+4,5-dichloroo-anisidine=N-(2-rnethoxy-4,5dichlorophenyl)-4-methoxy-Z,3,5-trichlorobe11zylamine.

EXAMPLE 13 Z-methoxy 5,6-dichlorobenzy1chloride+3,4,5-trichloroaniline=N (3,4,5-trichlorophenyl)-2methoxy-5,6-dichlorobenzylamine.

EXAMPLE 14 S-methoxy 4,6-dichlorobenzyl chloride-f-m-butoxyanL line=N(3-butoxyphenyl)-3-methoxy-4,6 dichlorobenzylamine.

EXAMPLE 15 4-methoxy-5,6-dichlorobenzyl chloride-I-p (butylthio)aniline=N-[4-(butylmercapto)phenyl] 4 methoxy-5,6- dichlorobenzylamine.

EXAMPLE 6 4 methoxy-Z,6-dichlorobenzylchloride-l-p-tert-butylaniline=N-(4-tertbutylphenyl)-4-methoxy-2,6-dichlorobenzylamine.

EXAMPLE 17 2 methoxy-S,6-dichlorophenethyl cl1loride+3,4dichloroaniline=N-(3,4-dichlorophenyl) 2 n1ethoxy-5,6-dichlorophenethylamine.

EXAMPLE 18 2-methoxy 3,5 dichlorobenzyl chloride'+p-aminophenol=N (4hydroxyphenyl)-2-methoxy-3,5-dichlorobenzylamine.

EXAMPLE 19 3-methoxy-2,6-dichlorobenzyl chloride+p-aminobenzenethiol=N(4 mercaptophenyl) 3 methoXy-2,6-dichlorobenzylamine.

For practical use as pesticides, the compounds of this invention aregenerally incorporated into herbicidal, insecticidal, and miticidalcompositions which comprise an inert carrier and a pesticidally toxicamount of such a compound. Such compositions, which are usually known inthe art as formulations, enable the active compound to be appliedconveniently to the site of the pest infestation in any desiredquantity. These compositions can be solids such as dusts, granules, orwettable powders; or they can be liquids such as solutions oremulsifiable concentrates.

For example, dusts can be prepared by grinding and blending the activecompound with a solid inert carrier such as the tales, clays, silicas,pyrophyllite, and the like. Granular formulations can be prepared byimpregnating the compound, usually dissolved in a suitable solvent, ontoand into granulated carriers such as the attapulgites or thevermiculites, usually of a particle size range of from about 0.3 to 1.5mm. Wettable powders, which can be dispersed in water to any desiredconcentration of the active compound, can be prepared by incorporatingwetting agents into concentrated dust compositions.

In some cases the active compounds are sufiiciently soluble in commonorganic solvents such as kerosene or xylene so that they can be useddirectly as solutions in these solvents. Frequently, solutions ofinsecticides can be dispersed under superatmospheric pressure asaerosols. However, preferred liquid compositions are emulsifiableconcentrates, which comprise an active compound according to thisinvention and as the inert carrier, a solvent and an emulsifier. Suchemulsifiable concentrates can be diluted with water to any desiredconcentration of active compound for application as sprays to the siteof the pest infestation. The emulsifiers most commonly used in theseconcentrates are nonionic or mixtures of nonionic with anionicsurface-active agents.

A typical composition according to this invention is illustrated by thefollowing example, in which the quantities are in parts by weight.

EXAMPLE Preparation of a dust Product of Example 3 10 Powdered talc 90The above ingredients are mixed in a mechanical grinder-blender and areground until a homogeneous, free-flowing dust of the desired particlesize is obtained. This dust is suitable for direct application to thesite of the pest infestation.

The pesticides of this invention can be applied in any manner recognizedby the art. The concentration of the new compounds of this invention inthe compositions will vary greatly with the type of formulation and thepurpose for which it is designed, but generally the compositions willcomprise from about 0.05 to about 95 percent by weight of the activecompounds of this invention. In a preferred embodiment of thisinvention, the compositions will comprise from about 5 to about 75percent by weight of the active compound. The compositions can alsocomprise such additional substances as other pesticides, Spreaders,adhesives, stickers, fertilizers, activators, synergists, and the like.

The new compounds of this invention can be used in many ways for thecontrol of insects and mites. Insecticides which are to be used asstomach poisons or protective materials can be applied to the surface onwhich the insects feed or travel. Insecticides which are to be used ascontact poisons or eradicants can be applied directly to the body of theinsect, as a residual treatment to the surface on which the insect maywalk or crawl, or as a fumigant treatment of the air which the insectbreathes. In some cases, the compounds applied to the soil or plantsurfaces are taken up by the plant, and the insects are poisonedsystematically.

The above methods of using insecticides are based on the fact thatalmost all the injury done by insects is a direct or indirect result oftheir attempts to secure food. Indeed, the large number of destructiveinsects can be classified broady on the basis of their feeding habits.There are, for example, the chewing insects such as the Mexican beanbeetle, the southern armyworm, cabbageworms, grasshoppers, the Colaradopotato beetle, the cankerworm, and the gypsy worm. There are also thepiercingsucking insects, such as the pea aphid, the house fly, thechinch bug, leafhoppers, and plant bugs.

Another group of insects comprises the internal feeders. These includeborers such as the European corn borer and the corn earworm; worms orweevils such as the codling moth, cotton boll weevil, plum curculio,melonworm, and the apple maggot; leaf miners such as the apple leafminer and the beet leaf miner; and gall insects such as the wheatjointworm and grape phylloxera. Insects which attack below the surfaceof the ground are classified as subterranean insects and include suchdestructive pests as the wooley apple aphid, the Japanese beetle, andthe corn rootworm.

Mites and ticks are not true insects. Many economically importantspecies of mites and ticks are known, including the red spider mite, thestrawberry spider mite, the cattle tick, and the poultry mite. Chemicalsuseful for the control of mites are often called miticides, while thoseuseful for the control of both mites and ticks are known specifically asacaricides.

The quantity of active compound of this invention to be used for insectcontrol will depend on a variety of factors, such as the specific insectinvolved, intensity of the infestation, weather, type of environment,type of formulation, and the like. For example, the application of onlyone or two ounces of active chemical per acre may be adequate forcontrol of a light infestation of an insect under conditions unfavorablefor its feeding, while a pound or more of active compound per acre maybe required for the control of a heavy infestation of insects underconditions favorable to their development.

Weeds are undesirable plants in their growing where they are not wanted,having no economic value, and interfering with the production ofcultivated crops or with the welfare of livestock. Many types of weedsare known, including annuals such as pigweed, lambsquarters, yellowfoxtail, crabgrass, wild mustard, Frenchweed, rye-grass, goose-grass,chickweed, and smartweed; biennials such as wild carrot, great burdock,mullein, round-leaved mallow, blue thistle, bull thistle, houndstongue,moth mullein, and purple star thistle; or perennials such as whitecockle, perennial rye-grass, quackgrass Johnson grass, Canada thistle,hedge bindweed, Bermuda grass, sheep sorrel, field chickweed, andwinter-cress. Similarly, such weeds can be classified as broad-leaf orgrassy weeds. It is economically desirable to control the growth of suchweeds without damaging beneficial plants or livestock.

The new compounds of this invention are particularly valuable for weedcontrol because they are toxic to many species and groups of weeds whilethey are relatively nontoxic to many beneficial plants. The method ofthis invention for the control of weeds comprises contacting said weedswith a herbicidal composition comprising an inert carrier and as theessential active ingredient, in a quantity which is herbicidally toxicto said weeds, a compound of this invention. The exact amount ofcompound required will depend on a variety of factors, including thehardiness of the particular weed species, weather, method ofapplication, the kind of beneficial plants in the same area, and thelike. Thus, while the application of up to only about one or two ouncesof an active compound per acre may be sufficient for good control of alight infestation of weeds growing under adverse conditions, theapplication of one pound or more of active compound per acre may berequired for good control of a dense infestation of hardy weeds growingunder favorable con ditions.

The herbicidal toxicity of the new compounds ofthis invention can beillustrated by many of the established testing techniques known to theart. For example, emulsifiable concentrate compositions can be dilutedwith water to concentrations equivalent to 4 pounds of the activecompound per acre. Duplicate paper pots filled with a sand and soilmoxture are seeded with weeds; and immediately atfer seeding, the soilsurface of each pot is sprayed with an appropriately diluted testsolution. The weed growth is maintained under artificial lighting withirrigation provided by placing the porous pots in a small amount ofwater in stainless steel trays. The Weeds are observed for a week to tendays; and the percent kill, injury, and stand reduction are recorded.The results indicate a high order of herbicidal activity of thecompounds of this invention. Comparable pre-planting or post-emergencetests can also be used.

What is claimed is:

1. A compound of the general formula in which n is a whole number from 1to 3; A, B, C, and D are selected from the group consisting of lowerunsubstituted alkoxy, chlorine, and hydrogen, at least 2 of A, B, C andD are chlorine, a maximum of 1 and a minimum of 2 of A, B, C, and D arelower unsubstituted alkoxy; and R is a phenyl radical substituted withfrom one to three substituents selected from the group consisting ofbromine, chlorine, lower unsubstituted alkyl, lower References Cited bythe Examiner UNITED STATES PATENTS 2,862,966 12/1928 Surrey 260--570.9XR 2,764,591 9/1956 Sprinzak 260570.9 XR 2,784,138 3/1957 Wegler et a1.260570.9 XR 2,962,531 11/1960 Coffield 260-5709 2,981,619 4/1961 Josephs712.3 3,070,628 12/1962 Lemin 260-5709 3,072,472 1/1963 Josephs 712.33,113,067 12/1963 Strufe et a1. 16730 OTHER REFERENCES Clemo et al.:Jour. Chem. Soc. London, 1953, pages 67883.

Forbes: Jour. Chem. Soc. London, 1956, pages 513- 17.

Kuehne et al.: Chemical Abstracts, vol. 54, pages 5502O5, (pages 5505relied on) (1960).

Sugasawa et 211.: Chemical Abstracts, vol. 50, pages 13913-14 (1956).

CHARLES B. PARKER, Primary Examiner.

JULIAN S. LEVITT, Examiner.

1. A COMPOUND OF THE GENERAL FORMULA